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Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway

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An Erratum to this article was published on 23 December 2011

Abstract

Fisetin is a naturally occurring flavonoid that has been reported to inhibit the proliferation and to induce apoptotic cell death in several tumor cells. However, the apoptosis-inducing effect of fisetin on tumor cell lines was investigated besides HeLa cells. In this study, we found that fisetin induced apoptosis of HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining of 4′-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI double-labeling. In addition, fisetin triggered the activations of caspases-3 and -8 and the cleavages of poly (ADP-ribose) polymerase, resulting in apoptosis induction. Moreover, treatment of HeLa cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059 (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector significantly abolished the fisetin-induced apoptosis through the activation of caspase-8/-3 pathway. The in vivo xenograft mice experiments revealed that fisetin significantly reduced tumor growth in mice with HeLa tumor xenografts. In conclusion, our results indicated that fisetin exhibited anti-cancer effect and induced apoptosis in HeLa cell lines both in vitro and in vivo.

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Acknowledgments

This work was supported by grants from National Science Council, Taiwan (NSC 98-2314-B-040-024) and Chung Shan Medical Hospital, Taichung, Taiwan (CSH-2011-C-026). Freeze centrifuge was performed in the Instrument Center of Chung Shan Medical University, which is supported by National Science Council, Ministry of Education and Chung Shan Medical University.

Conflict of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Tsung-Ho Ying

  2. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Shun-Fa Yang & Shu-Ching Hsieh

  3. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

    Shun-Fa Yang

  4. Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan

    Su-Ju Tsai

  5. Department of Physical Medicine and Rehabilitation, College of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Su-Ju Tsai

  6. Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, Taichung, Taiwan

    Yi-Chang Huang & Yi-Hsien Hsieh

  7. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan

    Da-Tian Bau

  8. Department of Biochemistry, School of Medicine, Chung Shan Medical University Clinical Laboratory, Chung Shan Medical University Hospital, No. 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan

    Yi-Hsien Hsieh

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  1. Tsung-Ho Ying
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Correspondence to Da-Tian Bau or Yi-Hsien Hsieh.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00204-011-0796-9

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Ying, TH., Yang, SF., Tsai, SJ. et al. Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway. Arch Toxicol 86, 263–273 (2012). https://doi.org/10.1007/s00204-011-0754-6

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  • DOI: https://doi.org/10.1007/s00204-011-0754-6

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